Induction of expression of MHC-class-II antigen on human thyroid carcinoma by wild-type p53.
Mutation of the tumor-suppressor gene p53 is involved in carcinogenetics. We investigated the role of p53 in the induction of anti-tumor immune responses by establishing a thyroid carcinoma cell line (1F3) prepared by transfection of wild-type human p53 gene into a p53-deficient cell line (FRO). Our results showed for the first time the involvement of p53 in the induction of anti-tumor immune responses, as demonstrated by: (i) expression of the major-histocompatibility-complex(MHC)-class-II antigen on 1F3, but not FRO; (ii) mRNA of class-II gene was expressed both in 1F3 and in FRO, but was stable at post-transcriptional level in FRO, which restrained protein synthesis; (iii) 1F3 induced MHC-class-II-specific CD4+ cytotoxic-T-cell activity through allo-antigen presentation and co-stimulation. Although our novel results are limited to the wild-type-p53-expressing clone from a p53-deficient cell line, we suggest that the absence of p53 in carcinoma cells may reduce the induction of CD4+ cytotoxic-T-cell activity against carcinoma cells by diminishing the expression of class-II antigen.
Zeki
K
K
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. kazuzeki@med.uoeh-u.ac.jp
Tanaka
Y
Y
Morimoto
I
I
Nishimura
Y
Y
Kimura
A
A
Yamashita
U
U
Eto
S
S
D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016158:Genes, p53 / Q000502:physiology*; D006682:HLA-DP Antigens / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D016219:Immunotherapy, Adoptive; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D004273:DNA, Neoplasm; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53